A major goal of the neuroscience community is to develop treatment strategies that will slow or forestall the progression of Parkinson's disease (PD). PD is one of the most common adult neurodegenerative disorders, affecting over 1 million people in North America and the European Union. As a first step, based on futility studies, the NINDS Exploratory Trials in Parkinson's disease (NET-PD) network identified creatine as a potential agent to slow clinical decline in PD. The NET-PD network is now conducting a large long term Phase III trial (LS-1) comparing creatine to placebo. During the renewal period the Statistical Coordination Center (SCC) proposes to complete the following specific aims in conjunction with the Clinical Coordination Center (CCC) and Clinical Sites in order to continue and complete LS1: Aim1 Test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. Given that PD is a multi-factorial disease that contributes to cognitive, motor, and behavioral disability, a gloal outcome measure of clinical decline analyzed by Global Statistical Test is utilized to provide sensitivity in detecting subtle overall changes in disease state; Aim 2 Test a set of secondary hypotheses to provide insight into the primary results; Aim 3 Continue as the SCC and (a) prepare interim reports for the CCC on performance of the Clinical Sites including retention, patient safety (blinded), and data quality; and (b) participate in the solution of problems with retention; Aim 4 Continue to (a) minimize bias and protect blinding during the entire project, (b) adjudicate outcome measures relating to efficacy and safety (as needed), and (c) provide periodic reports and interim analyses to the Data and Safety Monitoring Board (DSMB); Aim 5 In collaboration with the CCC and Clinical Sites (a) interpret and report results, and (b) document and archive the data in a publically available database. Aim 6 Maintain an administrative structure that allows close collaboration with the CCC, the clinical centers, NINDS Scientific Program personnel, the DSMB, and the NIH Oversight Board.